A Phase II Study of AK146D1 in Combination With AK112 in Advanced Non-Small Cell Lung Cancer

Inclusion criteria

• Be able to understand and voluntarily sign the written informed consent form.
• Aged of ≥ 18 years and ≤75 years.
• ECOG PS 0 or 1.
• The expected lifespan is ≥3 months.
• Patients with histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-small cell lung cancer (NSCLC) who are not eligible for curative surgical resection and cannot receive definitive concurrent or sequential chemoradiotherapy.
• At least one measurable non-brain lesion according to RECIST v1.1.
• Have sufficient organ function.
• Females subjects must not be pregnant at screening or have evidence of non-childbearing potential. Agree to use medically accepted methods of contraception.

Exclusion criteria

• NSCLC mixed with a component of small cell lung cancer, neuroendocrine carcinoma, or carcinosarcoma.
• Having other active malignancies within 3 years.
• Currently participating in another interventional clinical study.
• Presence of active metastases to the central nervous system. For patients with asymptomatic brain metastasis or stable symptoms after treatment can be included.
• Having received any treatment targeting Trop2 or Nectin4.
• Prior chemotherapy or antibody-drug conjugate (ADC) therapy targeting topoisomerase I inhibitors.
• Receipt of systemic anti-tumor therapy (including chemotherapy, immunotherapy, biological agents, etc.) within 4 weeks (or 5 half-lives of the drug, whichever is longer) prior to the first dose.
• Toxicity of previous antineoplastic therapy has not resolved to NCI CTCAE 6.0 grade 1 or lower.
• Subjects with clinically significant cardiovascular or cerebrovascular diseases or risks.
• Subjects with active autoimmune diseases requiring systemic treatment within 2 years.
• Receipt of systemic anti-infective therapy within 2 weeks prior to the first dose.
• Known to be positive for HIV and other infections.
• Previous history of severe hypersensitivity reactions.
• Live attenuated vaccines were received within 4 weeks.
• Subjects with a history of mental illness and incapacitated or limited capacity.
• Any disease or condition that, in the opinion of the investigator, would compromise subject safety or interfere with study assessments.